Sonobiopsy for Glioblastoma

Recruiting at 1 trial location

Overseen By Albert Kim, M.D., Ph.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Washington University School of Medicine

Disqualifiers: Previous cancer, Coagulopathy, Skull defect, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method called sonobiopsy to better understand and treat glioblastoma, a type of brain tumor. Sonobiopsy, or focused ultrasound-enabled liquid biopsy, combines ultrasound technology with a standard biopsy to gather detailed genetic information about the tumor. The goal is to improve treatment plans and outcomes for patients with brain lesions. This trial suits those recently diagnosed with a brain lesion resembling glioblastoma on a scan and who plan to undergo surgery to remove it. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could enhance future treatment strategies.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that sonobiopsy is safe for glioblastoma patients?

Previous studies have shown that sonobiopsy is safe for humans. Research found that this method, which uses ultrasound to collect tumor markers, is well-tolerated by patients with glioblastoma. Initial findings suggest that sonobiopsy does not cause major side effects, making it a promising tool for diagnosing brain diseases without surgery. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Sonobiopsy technique for glioblastoma because it offers a non-invasive way to gather crucial tumor information. Unlike traditional biopsies that require direct tissue extraction, Sonobiopsy uses a customized ultrasound probe and microbubbles to collect data, potentially reducing the risks associated with surgical biopsies. This method can provide real-time insights into the tumor's genetic makeup, which might help tailor personalized treatment plans more effectively. Additionally, it aims to improve the precision of tumor removal surgeries by offering enhanced imaging through MRI scans.

What evidence suggests that sonobiopsy is effective for glioblastoma?

Research has shown that sonobiopsy, the investigational treatment in this trial, is a promising new method for diagnosing brain conditions like glioblastoma. It uses focused ultrasound to release and detect tumor markers in the blood, simplifying the collection of crucial tumor information. Studies have found that this method is less invasive and precise in capturing tumor DNA. Early results suggest that sonobiopsy could offer a more sensitive and targeted approach to monitoring brain tumors, aiding doctors in understanding and treating these aggressive tumors more effectively. ^{1 5 6 7 8}

Who Is on the Research Team?

Albert Kim, M.D., Ph.D.

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for adults with a new diagnosis of glioblastoma, where the tumor is larger than 3 cm and close to the brain's surface. Candidates must be planning surgery to remove the tumor and have not had previous cancer treatments or cranial surgeries. People with MRI contraindications, skin diseases affecting ultrasound use, coagulopathy, metal in their head, or unstable heart/lung conditions cannot join.

Inclusion Criteria

I am scheduled for surgery to remove my tumor.

I have a recurring brain tumor confirmed by a recent MRI and am planning surgery.

My brain lesion is near the surface and in the upper part of my brain.

Exclusion Criteria

Ferrous material in the scalp or skull

Known hypersensitivity to polyethylene glycol

I do not have any recent serious heart or lung problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Sonobiopsy Procedure

Participants undergo the sonobiopsy procedure, which involves using a customized ultrasound probe and standard ultrasound contrast agent, followed by planned tumor removal surgery.

1 day

1 visit (in-person)

Post-Procedure Monitoring

Blood and possibly skin samples are collected for genetic analysis to compare against tumor mutations. An additional MRI scan is performed to assess imaging changes.

1-2 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the sonobiopsy procedure.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Sonobiopsy

Trial Overview

The study tests sonobiopsy—a noninvasive method that could help doctors understand brain tumors better by regularly collecting genetic and molecular information without surgery. This could lead to personalized treatment plans aimed at improving survival and life quality.

How Is the Trial Designed?

Group I: Sonobiopsy Experimental Treatment 4 Interventions

* Once enrolled, participants would be prepared for standard of care surgery. * The sonobiopsy involves the standard procedure for a biopsy, but the biopsy needle is replaced with a customized ultrasound probe, a standard ultrasound contrast agent (microbubbles) is injected intravenously, and the probe is turned on for 3 minutes for the sonobiopsy. Then the planned surgery to remove the tumor will occur. * An additional brief MRI scan will be obtained using the intraoperative MRI to define imaging changes (if any) that occur as a result of the sonobiopsy procedure. The imaging protocols will include a 3D T2-weighted (T2w) scan, and 3D contrast T1-weighted (T1w) with dynamic contrast enhancement and if time allows T2\* sequence. * Blood will be collected at several time points. * A small skin biopsy or another blood draw will be drawn for comparison against the genetic mutations shown in the tumor. * The blood, tumor, and skin (if applicable) will undergo genetic analysis.

Sonobiopsy is already approved in United States for the following indications:

Approved in United States as Sonobiopsy for:

• Glioblastoma
• Brain Tumors

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Low-frequency plane-wave ultrasound contrast imaging (1.5-4 MHz) significantly enhances the detection of microbubbles, yielding a contrast signal that is four times stronger at 1.8 MHz compared to 3.1 MHz, and nine times stronger than higher-frequency probes.

This imaging technique allows for the identification of sub-millimeter blood vessels in tumor models and provides better resilience to motion, suggesting its potential for super-resolution imaging and image-guided therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fast, Low-Frequency Plane-Wave Imaging for Ultrasound Contrast Imaging. Kusunose, J., Caskey, CF.[2023]

Using MRI-guided focused ultrasound (FUS) combined with microbubbles can effectively open the blood-brain barrier (BBB) and blood-tumor barrier (BTB), enhancing the delivery of brain-penetrating nanoparticle (BPN) gene therapies to brain tumors.

After FUS treatment, the flow of therapeutic agents through tumor tissue increased significantly, with interstitial flow velocity doubling and dispersion of BPNs improving by over 100%, indicating a promising method for improving gene therapy efficacy in brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Augmentation of brain tumor interstitial flow via focused ultrasound promotes brain-penetrating nanoparticle dispersion and transfection. Curley, CT., Mead, BP., Negron, K., et al.[2023]

In a phase I study involving 5 patients with high-grade glioma, MR-guided focused ultrasound (MRgFUS) was successfully used to temporarily open the blood-brain barrier (BBB) without surgery, allowing for enhanced delivery of chemotherapy.

The procedure was safe and well-tolerated, showing no adverse effects, and resulted in a significant increase in chemotherapy delivery to the targeted brain tissue, indicating its potential for improving treatment efficacy in brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blood-Brain Barrier Opening in Primary Brain Tumors with Non-invasive MR-Guided Focused Ultrasound: A Clinical Safety and Feasibility Study. Mainprize, T., Lipsman, N., Huang, Y., et al.[2020]

The first-in-human trial of sonobiopsy in glioblastoma patients demonstrated its feasibility and safety, successfully enhancing circulating tumor biomarker levels in blood samples after focused ultrasound treatment.

Histological analysis confirmed the procedure's safety, showing minimal inflammatory response and modulation of specific genes related to cell structure, supporting further research into sonobiopsy for noninvasive brain disease diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-human prospective trial of sonobiopsy in glioblastoma patients using neuronavigation-guided focused ultrasound. Yuan, J., Xu, L., Chien, CY., et al.[2023]

The first-in-human trial of sonobiopsy in high-grade glioma patients demonstrated its feasibility and safety, successfully enriching plasma circulating tumor DNA (ctDNA) after focused ultrasound treatment.

Sonobiopsy significantly increased levels of specific tumor biomarkers in the blood, including a 5.6-fold increase in TERT mutation ctDNA, indicating its potential for noninvasive molecular diagnosis of brain diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-human prospective trial of sonobiopsy in high-grade glioma patients using neuronavigation-guided focused ultrasound. Yuan, J., Xu, L., Chien, CY., et al.[2023]

Ultrastable lipid-coated microbubbles serve as an effective ultrasonic contrast agent for brain imaging, enhancing the visibility of gliomas for up to 1 hour after intravenous administration.

These microbubbles allow for earlier detection of brain tumors, visualizing lesions 40% sooner than traditional methods, and improve the signal-to-noise ratio during ultrasound scans, indicating their potential for better diagnostic accuracy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative assessment of tumor enhancement by ultrastable lipid-coated microbubbles as a sonographic contrast agent. Simon, RH., Ho, SY., Perkins, CR., et al.[2019]

Transcranial microbubble-enhanced focused ultrasound (MB-FUS) safely and effectively opens the blood-brain barrier (BBB) in patients with infiltrating gliomas, as demonstrated in a Phase 0 clinical trial with MRI and histopathology confirming reproducible results.

The study found a significant increase in drug accumulation in treated tumor tissues, with a 2.2-fold increase in fluorescein compared to untreated areas, suggesting that MB-FUS could enhance the delivery of therapeutics for better treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Localized blood-brain barrier opening in infiltrating gliomas with MRI-guided acoustic emissions-controlled focused ultrasound. Anastasiadis, P., Gandhi, D., Guo, Y., et al.[2022]

Focused ultrasonography can effectively disrupt the blood-brain barrier, which is a major challenge in delivering chemotherapy to glioblastoma tumors, potentially enhancing the efficacy of treatment.

The review discusses both preclinical and clinical studies that support the use of focused ultrasonography to improve the delivery of oncotherapeutic agents, suggesting a promising future for this technique in glioblastoma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focused Ultrasonography-Mediated Blood-Brain Barrier Disruption in the Enhancement of Delivery of Brain Tumor Therapies. Zaki Ghali, MG., Srinivasan, VM., Kan, P.[2020]

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Glioblastoma is the most prevalent malignant primary brain tumor in adults, with a five-year survival rate of less than eight percent [3]. In children, brain ...

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This clinical study to evaluate sonobiopsy is significant because sonobiopsy will fundamentally enhance the clinician's insight into the molecular features of ...